Transtornos menstruales

Menstrual Disorders
Susan Hayden Gray
Pediatrics in Review 2013;34;6
DOI: 10.1542/pir.34-1-6

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Article genital system disorders

Menstrual Disorders
Susan Hayden Gray, MD*
Practice Gap
1. Dysmenorrhea, amenorrhea, and abnormal vaginal bleeding affect the majority of
Author Disclosure adolescent females, impacting quality of life and school attendance. Patient-centered
Dr Gray has disclosed adolescent care should include searching for, assessing, and managing menstrual concerns.
no financial 2. Polycystic ovary syndrome (PCOS) is the most common endocrinopathy in young
relationships relevant adult women, and pediatricians should recognize, monitor, educate, and manage their
to this article. This patients who fit the medical profile for PCOS based on any/all of the three sets of
commentary does diagnostic criteria.
contain a discussion of
an unapproved/
Objectives After reading this article, readers should be able to:
investigative use of
a commercial product/ 1. Define primary and secondary amenorrhea and list the differential diagnosis for each.
device. 2. Recognize the importance of a sensitive urine pregnancy test early in the evaluation of
menstrual disorders, regardless of stated sexual history.
3. Know that polycystic ovary syndrome is a common cause of secondary amenorrhea in
adolescents and may present with oligomenorrhea or abnormal uterine bleeding.
4. Recognize that eating disordered behaviors are a common cause of secondary amenorrhea
and irregular bleeding, and treatment of the eating disordered behavior is the best
recommendation to ensure resumption of regular menses and long-term bone health.
5. Know the differential diagnosis of abnormal uterine bleeding and describe the
preferred treatment, recognizing the central importance of iron replacement.
6. Understand the prevalence of primary dysmenorrhea and its role in causing recurrent
school absence in young women, and describe its evaluation and management.
7. Understand the need for discussion of menstrual and reproductive health with young
women who have special health-care needs and their families.
The onset of menstruation in young women is a milestone with personal, cultural, and
medical ramifications. Menarche heralds the onset of fertility, which can be cause for both
celebration and trepidation for the patient, her family, and
clinicians. It behooves both general and specialist pediatri-
cians to be comfortable discussing what is normal and what
Abbreviations: is not normal about menstruation. Young women who have
AIS: androgen insensitivity syndrome special health-care needs and their families deserve particular
DHEAS: dehyroepiandrosterone-sulfate attention. Both the American Academy of Pediatrics and the
FSH: follicle stimulating hormone American College of Obstetricians and Gynecologists en-
GnRH: gonadotropin-releasing hormone courage pediatricians to think of menstruation as a “vital
IUD: intrauterine device sign” for women. (1)(2) Irregular, absent, or overly painful
LH: luteinizing hormone periods should be evaluated, closely monitored, and man-
MRKH: Mayer-Rokitansky-Küster-Hauser syndrome aged proactively.
NSAID: nonsteroidal anti-inflammatory drug
OCP: oral contraceptive Patient-Centered Care of Menstrual Disorders
PCOS: polycystic ovary syndrome In both the evaluation and treatment of menstrual disorders,
TSH: thyroid stimulating hormone it is critical to keep in mind the patient’s perspective on her
symptoms. It is extremely valuable to hear from the patient

*Clinical Instructor in Pediatrics, Harvard Medical School; Attending Physician, Division of Adolescent and Young Adult Medicine,
Boston Children’s Hospital, Boston, MA.

6 Pediatrics in Review Vol.34 No.1 January 2013

genital system disorders menstrual disorders

what her expectations of menses are, and where she has It was thought previously that hypothalamic axis im-
derived these expectations. In conditions ranging from maturity in the first gynecologic year was common, and
polycystic ovary syndrome (PCOS) to endometriosis, the therefore menstrual irregularity was to be expected.
patient’s quality of life has been shown to be much more More current data indicate that even in the first gyne-
strongly linked to her own perception of her symptoms cologic year, amenorrhea for more than 3 months is un-
than to her doctors’ assessment of their severity. Periods common in healthy girls in the United States and
perceived as heavy, painful, or abnormal can be a signifi- should be investigated if there are other issues apparent,
cant cause of school absence and decreased work produc- or if the pattern persists into the second year. A normal
tivity. What many patients and families desire as much as menstrual cycle (counting from the first day of one
relief from menses or menstrual pain is predictability. Set- menstrual period to the first day of menses of the next
ting realistic expectations from the onset of medical treat- cycle) is 21 to 35 days in adults but has a slightly wider
ment goes a long way in improving quality of life. range of normal in adolescents during the first 2
The presence of menses can be a challenge to the fam- years after menarche. A normal period lasts from 3 to
ilies of young women who have special health-care needs, 7 days. Bleeding lasting 8 or more days is considered
and particular sensitivity is warranted. The onset of men- prolonged.
struation may raise what can be uncomfortable questions
about fertility and sexual activity (voluntary or otherwise)
for the families of these young women. Patients and fam- Review of Menstrual Physiology
ilies appreciate and deserve the opportunity to talk openly The menstrual cycle is divided commonly into three
about these subjects. phases: follicular (proliferative), ovulation, and luteal (se-
cretory) (Figure). The follicular phase may vary in length,
Epidemiology/Normal Menses but the luteal phase is 14 days during normal ovulatory
The median age of menarche in the United States is 12.4 cycles. Ovulation is the event that defines regular cycles
years, with African-American girls experiencing menarche and triggers the prostaglandin cascade, which is associ-
slightly earlier on average than non-Hispanic white and ated with primary dysmenorrhea.
Mexican-American girls, as determined in the third Na- Gonadotropin-releasing hormone (GnRH) secretion
tional Health and Nutrition Evaluation Survey. (3) The in the hypothalamus is pulsatile and stimulates the pitu-
usual sequence of events leading up to menarche includes itary gland to secrete luteinizing hormone (LH) and fol-
thelarche (Tanner [sexual maturation rating] stage 2 breast licle stimulating hormone (FSH), which stimulates
development) at a median age of 10.2 years and pubarche follicle growth in the ovary. A dominant follicle in the
(Tanner stage 2 pubic hair) at a median age of 11.6 years, ovary secretes increasing amounts of estrogen, which
but recent studies have revealed that girls are developing causes the endometrial lining to proliferate. A feedback
breasts and pubic hair earlier than in past generations al- loop develops in which increasing amounts of estrogen
though the age of menarche has remained more constant. result in decreasing LH and FSH levels; but above a cer-
(4) Some girls, particularly African-American girls, may ex- tain estrogen level, the negative feedback is reversed and
perience pubarche before thelarche. Early pubarche, espe- LH release from the pituitary is stimulated. This “LH
cially accompanied by obesity and insulin resistance, is surge” triggers ovulation.
associated with later development of PCOS. After ovulation, the remaining follicular cells in the
The definition of precocious puberty remains controver- ovary luteinize and become the corpus luteum. This cor-
sial because of mixed data about how ethnicity and adiposity pus luteum secretes estrogen and progesterone, which
affect development. Generally, the presence of breast devel- has the effect of stabilizing the endometrium and causing
opment or pubic hair before age 8 years is considered pre- differentiation into glandular tissue to produce the
cocious, although girls whose BMI is greater than 85% or spongy lining needed for implantation of a fertilized
who are African-American or Mexican-American may have ovum. If fertilization and implantation do not occur, hu-
earlier development. In one study, 27% of African-American man chorionic gonadotropin is not produced, and the
girls had signs of pubertal development at age 7 years, com- corpus luteum involutes. The withdrawal of progesterone
pared with 7% of white girls. (5) Menarche occurring after (and estrogen) levels derived from the corpus luteum is
age 14.1 years occurs in only 5% of girls in the United States; the trigger for the shedding of the endometrial lining,
the definition of primary amenorrhea is failure to achieve or menses. In anovulatory girls, menstrual periods occur
menarche by age 15 years. Failure to progress from thelarche from a proliferative endometrium because of waxing and
to menarche within 3 years is also cause for concern. waning of estrogen levels.

Pediatrics in Review Vol.34 No.1 January 2013 7


eating patterns and weight changes are among the most
common reasons for amenorrhea. Review of a growth
chart is important in considering the possible causes.
The differential diagnosis of primary amenorrhea in-
cludes genital tract abnormalities, as well as endocrine
causes (which also may cause secondary amenorrhea), in-
cluding hypothalamic/pituitary, ovarian, thyroid, or ad-
renal abnormalities. The assessment of the patient should
include a detailed history and physical examination, lab-
oratory testing, and radiologic imaging in some cases.
The patient and parent should be asked about a past
medical history of chronic illness, tempo of any pubertal de-
velopment, weight gain or loss, exercise habits, and stressors.
Family history should focus on any potential endocrine dis-
orders in first-order relatives, including thyroid disease, dia-
betes, PCOS, and infertility. The parent should be asked also
about any family history of constitutional delay of menses.
Sexual history should be obtained confidentially, because
pregnancy is a rare but possible cause of primary amenorrhea
and the most common cause of secondary amenorrhea.
Social stressors may contribute to primary or secondary
amenorrhea, and asking about academic pressure, family
conflict, mood disorders, body image, and eating behaviors
is important. Clinicians should ask about history of medica-
tion use, including any antipsychotic medication, contracep-
tive use (adolescents often forget or deny use unless asked
specifically), and illicit drug use. The review of systems
should include discussion of acne or unwanted hair growth,
weight changes, mood changes, disordered eating attitudes
and behavior, change in bowel habits, abdominal pain, head-
aches, visual changes, galactorrhea, and vaginal discharge.
Figure. The normal menstrual cycle, with relationship among The review of a growth chart identifies patients who are
levels of gonadotropins, physiologic activity in the ovary, overweight or underweight for height. Girls who are over-
levels of ovarian steroids, and changes in the endometrium. weight for height and not growing appropriately are more
Reprinted with permission from Braverman PK, Sondheimer likely to have an endocrinopathy (hypothyroidism, Cush-
SJ. Menstrual disorders. Pediatr Rev. 1997;18(1):18. ing syndrome), whereas patients underweight for height
may have a deficit of calories (eating disorder or bowel dis-
Amenorrhea ease such as inflammatory bowel disease or celiac disease).
Primary amenorrhea is clinically defined as the lack of The patient who has exceptionally short stature (final
menses by the age of 15 years or by more than 3 years height predicted to be less than 5 ft in the patient who has
after the onset of secondary sexual development. Lack normal parental heights), with or without other features
of any secondary sexual characteristics by age 13 years such as webbed neck, widely spaced nipples, shield chest,
also is abnormal and should be investigated. Secondary and high arched palate, and primary amenorrhea raises
amenorrhea is defined as 3 months of amenorrhea after concerns about Turner syndrome (45,X) or mosaicism
the achievement of menarche. Underlying conditions may (46,XX/45,X). Consultation with a geneticist or endo-
overlap in primary and secondary amenorrhea (Table 1). crinologist may be warranted.
Careful history and physical examination are crucial to Physical examination should include assessment of
diagnosis. It cannot be overstated, however, that a sensi- height, weight, and BMI in addition to routine vital signs.
tive pregnancy test must be part of the initial evaluation The clinician should examine the patient’s skin thor-
of any patient with amenorrhea, regardless of the re- oughly. Peripheral visual fields should be checked by con-
ported sexual history. Besides pregnancy, disordered frontation and the fundi examined. The clinician should



Table 1. Differential Diagnosis of Amenorrhea
Primary Amenorrhea Secondary Amenorrhea
a
Central (hypothalamus/pituitary; Constitutional delay Functional hypothalamica
hypogonadotropic hypogonadism Chronic illnessa amenorrhea
with low FSH) Functional hypothalamic Chronic illness
amenorrheaa Tumors (prolactinoma)
Kallmann syndrome
Laurence-Moon-Biedl and
Prader-Willi syndromes
Tumors (craniopharyngioma
and prolactinoma)
Infiltration (hemochromatosis)
Infarction
Iatrogenic (radiation, surgery)
Congenital hypopituitarism
Ovarian (hypergonadotropic Turner syndromea Primary ovarian insufficiency
hypogonadism with high FSH) Gonadal dysgenesis Oophoritis
Primary ovarian insufficiency Radiation, chemotherapy
Oophoritis
Galactosemia
Tumor
Radiation, chemotherapy
Genital outflow tract Imperforate hymena Uterine synechiae (Asherman
MRKHa syndrome)
Transverse vaginal septum
Vaginal agenesis
Androgen insensitivity
Intersex disorders
Other Pregnancy Pregnancya
PCOS (uncommon) PCOSa
Thyroid disease Contraceptive use
Cushing syndrome Hyperprolactinemia due to
Addison disease medication or illicit drug use
Thyroid disease
Late-onset congenital adrenal
hyperplasia
Cushing syndrome
Addison disease
a
Most common diagnosis in each category; the other diagnoses are not listed in order of prevalence.

test for, or at least ask about, the presence of smell (anos- woman). If there is any question of an anatomic abnor-
mia is associated with Kallmann syndrome). The thyroid mality, pelvic ultrasonography should be performed at
gland should be palpated for enlargement. Tanner staging a center experienced with prepubertal patients.
should be recorded and tracked over time, and breast ex-
amination should verify whether there is any galactorrhea. Genital Outflow Tract Anomalies
Abdominal palpation should be performed to detect con- The range of congenital abnormalities includes external
stipation or the presence of any masses. anomalies such as imperforate hymen and transverse vag-
An external genital evaluation should be performed to inal septum with normal müllerian structures, as well as
detect clitoromegaly (clitoral glans wider than 0.5 cm) müllerian anomalies such as uterine and vaginal agenesis.
and patency of the introitus. All that is necessary for an Appropriate and consistent visual examination of the vag-
internal examination in virginal patients may be passage inal introitus in the newborn and at health maintenance
of a saline moistened cotton-tip swab to assess the depth visits should prevent the late diagnosis of imperforate hy-
of the vagina (7–8 cm is average for a postpubertal young men. Early detection can help avoid the “classic”



presentation of imperforate hymen in a postpubertal young for girls who experience secondary amenorrhea. Because
woman: cyclic abdominal pain, midline abdominal mass, pregnancy is a common cause for secondary amenorrhea,
and purplish bulging seen at the introitus of the vagina the first test to perform is a sensitive urine pregnancy
(a hematocolpos, which may be remarkably large). Such test. The next steps are to obtain levels of FSH, LH,
late-found cases require gynecologic intervention in an op- thyroid stimulating hormone (TSH) or free thyroxine,
erating room or controlled setting, as opposed to a simpler and prolactin. Other laboratory tests to consider include
procedure when the patient is diagnosed as a newborn. levels of androgen (total and free testosterone and
Transverse vaginal septum presents similarly but may dehydroepiandrosterone-sulfate [DHEAS]) to screen
be harder to identify because the external examination for hyperandrogenism, and possibly pelvic ultrasonogra-
may appear normal. A swab cannot be passed a normal phy. Free testosterone levels should only be drawn if
length in the presence of a low transverse septum, but the laboratory is known to provide high quality results.
a high septum may not be detected without direct visu- Elevated levels of FSH indicate hypergonadotropic hypo-
alization or pelvic imaging. gonadism, whereas low levels indicate hypogonadotropic
Vaginal agenesis rarely occurs as an isolated finding and hypogonadism.
usually is associated with other müllerian anomalies. Mayer- Hypergonadotropic hypogonadism implies ovarian
Rokitansky-Küster-Hauser syndrome (MRKH) includes insufficiency, and the most common cause is gonadal
vaginal agenesis and, usually, uterine and fallopian tube dysgenesis, most frequently due to Turner syndrome.
agenesis as well. On external examination, the vaginal open- Turner syndrome usually presents with delayed puberty
ing ends in a blind pouch. Girls with MRKH go through and primary amenorrhea, but secondary amenorrhea is
puberty at the usual tempo because they have normal ova- possible, especially in patients born with a mosaic chro-
ries, but they do not attain menarche. Because they have mosome pattern. Other causes of ovarian insufficiency
normal ovaries, they can have children by oocyte retrieval, include autoimmune and radiation- or chemotherapy-
fertilization of the egg in vitro, and a gestational carrier. induced oophoritis, as well as galactosemia. Autoimmune
Young women born with androgen insensitivity syn- oophoritis may be associated with other autoimmune
drome (AIS) are genetically males (46,XY), but their andro- conditions, such as diabetes mellitus, adrenal insuffi-
gen receptors do not respond to testosterone in the usual ciency, thyroid disease, celiac disease, and vitiligo.
way. They have serum levels of testosterone comparable Hypogonadotropic hypogonadism implies that either
with adolescent males, but do not have body hair and do the hypothalamus or the pituitary gland is the root of the
have breast development due to peripheral aromatization to problem. The most common cause of hypogonadotropic
estrogen. Because they are 46,XY, they possess müllerian hypogonadism is functional hypothalamic amenorrhea,
inhibitory substance, which inhibits formation of the uterus but this is a clinical diagnosis, and a diagnosis of exclu-
and vagina. Although they have female-appearing external sion, so diagnostic evaluation, including levels of FSH,
genitalia, they possess testes, which most patients elect to LH, TSH, and prolactin, is warranted as well as screening
have surgically removed after puberty because of the in- for eating disorders and sometimes for celiac diseases.
creased risk of cancer. There are rare, partial forms of Although rare, tumors may impinge on the pituitary, so
AIS in which female patients present as somewhat virilized. it is important to ask all patients about the occurrence of
Patients with vaginal agenesis are able to create a vagina headaches, visual changes, and galactorrhea, and to check
with the use of manual dilators with expert coaching and for galactorrhea on examination. The most common pitu-
education. The young woman must be able to choose itary tumor is a prolactinoma. A craniopharyngioma also
whether she wants to and, if so, at which age she wishes can present with poor growth and amenorrhea, as can
to begin. Although there are surgical procedures such as pituitary infiltration by hemochromatosis.
bowel vaginas and other complex approaches, the draw- Laurence-Moon-Biedl and Prader-Willi syndromes
backs are excess vaginal discharge and the need for ongo- present with obesity, developmental delay, and amenor-
ing dilatation. Online resources and support groups, such rhea due to hypothalamic dysfunction. Kallmann syn-
as at www.youngwomenshealth.org, may provide a needed drome presents as amenorrhea with anosmia. Kallmann
source of information and emotional support for girls with syndrome is a disorder of neuronal migration, whereby
MRKH, AIS, and other rare conditions. GnRH neurons do not migrate to the hypothalamus;
thus, the olfactory bulbs also do not develop properly.
Other Causes of Amenorrhea Functional hypothalamic amenorrhea, or secondary
For girls with primary amenorrhea unrelated to outflow amenorrhea due to suppression of GnRH pulsatility in
tract anomalies, the diagnostic evaluation is similar to that which no anatomic or organic disease is known, can be



caused by stress, weight loss, or exercise. This condition pediatric clinicians use one of these two definitions, with
may result in a low estrogen state, which places young clinical or biochemical hyperandrogenism being sine
women at risk for failure to achieve peak bone mass. This qua non.
disorder is often, but not always, associated with being Evaluation for PCOS includes measuring LH, FSH,
underweight and with eating disorders. Secondary amen- TSH, and prolactin levels to exclude other disorders, as
orrhea may precede significant weight loss in anorexia well as obtaining serum levels of testosterone (a normal
nervosa, and weight gain beyond the point where menses total testosterone excludes a testosterone-producing tu-
were lost frequently is required for resumption of menses. mor), free testosterone (elevated in most patients with
Normal-weighted bulimic patients who are purging fre- PCOS), and DHEAS.
quently also may experience amenorrhea. In patients with virilization (eg, clitoromegaly, deep
Female athletes are at risk for developing the “female voice, notable hirsutism), a first morning 17-hydroxypro-
athlete triad,” consisting of energy insufficiency, amenor- gesterone to rule out late-onset congenital adrenal hyper-
rhea, and low bone density. Use of oral contraceptives plasia and evaluation for a tumor is warranted. Pelvic
(OCPs) can induce withdrawal bleeding but has not been ultrasonography may be a useful adjunct to laboratory
shown to be effective at increasing bone density in ath- testing, although ideally the procedure should be per-
letes or in those with anorexia nervosa. formed in a center with pediatric expertise. In the case
The role of leptin is being investigated actively, be- of significantly elevated concentrations of DHEAS or to-
cause leptin administration recently has been demon- tal testosterone, other androgen levels, such as androste-
strated to promote resumption of menses. Trials of nedione and dehydroepiandrosterone, may be drawn,
androgens and estrogens together and transdermal estro- and consultation with an endocrinologist is suggested.
gen alone have demonstrated promising effects in small In rare situations of high testosterone levels combined
studies. Increased energy availability, meaning weight with genital anomalies, chromosome studies should be
gain in most cases, has been shown to have long-term considered to rule out intersex conditions.
and significant positive effects on bone density. PCOS is associated with abnormal LH pulsatility and
Because of the serious long-term sequelae for bone secretion beginning in the premenarchal period, ulti-
health, young women with prolonged functional hypo- mately resulting in increased androgen production from
thalamic amenorrhea who do not or will not increase the ovaries and adrenal glands, as well as anovulation. Be-
their energy availability should be referred for multidisci- cause anovulation leads to irregular buildup of the endo-
plinary assessment to a nutritionist, a mental health pro- metrial lining, the initial presentation of PCOS may be as
fessional, and a health-care provider who are well versed heavy (previously known as dysfunctional) uterine bleeding.
in eating disorders and bone health. (6) PCOS is associated with insulin resistance in more
PCOS is the most common endocrinopathy in young than one half of patients and is an independent risk factor
adult women; some researchers estimate that the condi- for later development of type II diabetes and the meta-
tion affects up to 10% of American women of reproduc- bolic syndrome. Current recommendations are that pa-
tive age. Young women with PCOS present with tients who have PCOS and an elevated BMI should
amenorrhea or oligomenorrhea and signs of hyperandro- undergo lipid testing and an oral glucose tolerance test
genism, including hirsutism and acne. They are often, but every 1 to 2 years.
not always, overweight. Because of prolonged periods of unopposed estrogen
There are three sets of criteria for diagnosis of PCOS: stimulation and endometrial proliferation resulting from
the 1990 National Institutes of Health consensus criteria, anovulation, older women with PCOS also are at in-
the 2003 Rotterdam criteria, and the 2006 Androgen Ex- creased risk of endometrial cancer. This risk can be re-
cess Society criteria. (7)(8)(9) The National Institutes of duced through early detection and treatment to ensure
Health criteria include patients with anovulatory menses more regular endometrial shedding. Lifestyle modifica-
and clinical or biochemical evidence of hyperandrogenism, tion including exercise and weight loss can improve men-
with or without polycystic ovaries on ultrasonography, strual regularity in some women.
in whom other diagnoses (eg, late-onset congenital adre- Pharmacologic treatment for PCOS includes three op-
nal hyperplasia and thyroid disease) have been excluded. tions: cyclic use of progestins to induce withdrawal bleed-
The Androgen Excess and PCOS Society guidelines ing; use of estrogen-containing contraceptives (pills,
also include those patients who experience normal menses transdermal patch, or vaginal ring) to reduce ovarian an-
but have biochemical or clinical hyperandrogenism drogen production and increase steroid hormone binding
and also polycystic ovaries on ultrasonography. Most globulin; and use of metformin to lower circulating



insulin levels and reduce ovarian steroid hormone such as ectopic pregnancy and miscarriage), bleeding dis-
production. orders, pelvic infection, and endocrinopathies such as
It is important to note the potential reproductive ram- PCOS and thyroid disease.
ifications of these therapies. Estrogen-containing contra- In evaluating the patient with abnormal vaginal bleed-
ceptives are the best option for sexually active young ing, it is important to consider the possibility of preg-
women who do not desire a pregnancy and those with nancy first, because pregnancy complications presenting
hirsutism and acne; metformin use is particularly helpful with bleeding, such as ectopic pregnancy, can be life
for those with glucose intolerance. Metformin promotes threatening. All patients should be asked privately
ovulation, so this drug should not be the sole therapy in whether they have ever had sex, coerced or voluntary,
sexually active teenagers. Some young women choose to but pregnancy testing should be obtained universally be-
use both therapies. Spironolactone often is used as an ad- cause patients may fear the consequences of disclosure.
junct treatment to reduce androgen effects on the hair Patients who have ever had sex should be asked specifi-
follicle in girls with hirsutism; spironolactone’s use as cally about contraceptive use and about history of any
monotherapy is not recommended because it is terato- sexually transmitted infections, and should be tested
genic and causes menstrual irregularity unless used in for gonorrhea and Chlamydia trachomatis infection by
conjunction with an estrogen-containing contraceptive. using simple urine nucleic acid amplification tests. Re-
gardless of stated history, pediatricians should have
a low threshold for performing these tests for unex-
Abnormal Vaginal Bleeding plained bleeding because the prevalence of Chlamydia
Abnormal vaginal bleeding is reported commonly during is so high in adolescent women.
adolescence. Pediatric practitioners must know what is The patient’s menstrual history can then help narrow
normal in order to assess patients accurately. A normal down other possibilities. Patients should be asked about
period usually lasts 3 to 7 days. Bleeding that lasts 8 days the date of menarche and the pattern of bleeding since
or longer is considered abnormal. The normal interval that time. For patients who have had heavy flow from
between menses in adolescents may be between 21 and the time of initial menses, a bleeding disorder such as
45 days in young adolescents, although 21 to 35 days von Willebrand disease is more likely. Regular cycles ac-
is more common. companied by premenstrual symptoms and dysmenor-
Menorrhagia means a large quantity of bleeding, me- rhea usually imply ovulatory bleeding. Regular, cyclic,
trorrhagia means irregular bleeding, and menometror- but heavy flow is suggestive of a hematologic cause. Ir-
rhagia means heavy and irregular bleeding. When regular cycles suggest anovulatory cycles, which may be
patients say that they have “heavy” bleeding, however, due to an underlying endocrinopathy such as PCOS or
it is important to ask them whether they mean bleeding hypothyroidism, a condition that causes functional hypo-
that is in large quantity, frequent, or associated with pain, thalamic amenorrhea. Intermenstrual bleeding suggests
because these symptoms have different implications. anatomic disease (cervicitis due to sexually transmitted
Studies reveal that both adolescent patients and their infections must be ruled out) or breakthrough bleeding
clinicians can significantly underestimate as well as over- associated with use of hormonal contraception.
estimate the amount of vaginal bleeding, so it is impor- The review of symptoms should include questions
tant to obtain objective evidence of blood loss regardless about weight changes, exercise habits, bleeding tendencies,
of the history (eg, complete blood count). acne, hirsutism, headaches, visual changes, chronic illness,
The differential diagnosis of abnormal vaginal bleed- bowel habits, and urinary symptoms (younger patients may
ing is broad (Table 2). The term “dysfunctional uterine confuse hematuria with vaginal bleeding). Family history
bleeding” has been replaced by “abnormal uterine bleed- of bleeding tendencies (especially during childbirth
ing.” Abnormal uterine bleeding refers to irregular and and surgical procedures), endocrinopathies, and infertil-
sometimes heavy bleeding due to a delay in maturation ity should be elicited. Patients should be asked specifically
of the negative feedback loop whereby rising estrogen (and confidentially) about contraceptive use, including
levels suppress FSH secretion. This maturational delay re- intrauterine devices (IUDs). Clinicians also should ask
sults in a constantly proliferative endometrium with irreg- about antipsychotic and antiepileptic medications that
ular shedding. Abnormal uterine bleeding is the most may cause irregular bleeding, and aspirin and other anti-
common cause of abnormal bleeding in adolescents, but coagulants, which may worsen bleeding.
it is a diagnosis of exclusion, and the differential diagnosis Physical examination should include orthostatic vital
also should include pregnancy (including complications signs for those with heavy bleeding. Young women



Differential Diagnosis of Abnormal Vaginal Bleeding in the
Table 2.

Adolescent Girl
Abnormal uterine bleeding Cervical problems
Cervicitis (including cystic fibrosis)
Pregnancy-related complications Polyp
Threatened abortion Hemangioma
Spontaneous, incomplete, or missed abortion Carcinoma or sarcoma
Ectopic pregnancy
Gestational trophoblastic disease Uterine problems
Complications of termination procedures Submucous myoma
Congenital anomalies
Infection Polyp
Pelvic inflammatory disease Carcinoma
Endometritis Use of intrauterine device
Cervicitis Breakthrough bleeding associated with
Vaginitis hormonal contraceptives
Ovulation bleeding
Bleeding disorders
Thrombocytopenia (eg, idiopathic Ovarian problems
thrombocytopenic purpura, leukemia, Cyst
aplastic anemia, hypersplenism, chemotherapy) Tumor (benign, malignant)
Coagulation disorders (eg, von Willebrand
disease, other disorders of platelet function, Endometriosis
liver dysfunction, vitamin K deficiency)
Trauma
Endocrine disorders
Hypo- or hyperthyroidism Foreign body (eg, retained tampon)
Adrenal disease
Hyperprolactinemia Systemic diseases
PCOS Diabetes mellitus
Primary ovarian insufficiency Renal disease
Systemic lupus erythematosus
Vaginal abnormalities
Carcinoma or sarcoma Medications
Laceration Hormonal contraceptives
Anticoagulants
Platelet inhibitors
Androgens
Spironolactone
Antipsychotics
Reprinted with permission from Gray SH, Emans SJ. Abnormal vaginal bleeding in the adolescent. In: Emans SJ, Laufer MR, eds. Emans, Laufer, and
Goldstein’s Pediatric and Adolescent Gynecology. 6th ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2011:159–167.

may be remarkably tolerant of severe anemia and show no bleeding or bleeding resulting in anemia, assessment
signs other than resting tachycardia or orthostatic hypo- can be managed by external genital examination with pas-
tension. Providers should examine the skin for acne, hir- sage of a cotton-tip swab to assess vaginal patency, as well
sutism, and acanthosis nigricans suggestive of PCOS as as transabdominal pelvic ultrasonography.
well as petechiae or bruising to suggest bleeding disor- Laboratory testing should consist initially of a urine
ders. The thyroid gland should be palpated. Palpation pregnancy test and a complete blood count, including
of the abdomen should begin in the epigastric area and platelet and reticulocyte count, and TSH level. In both
progress downward, assessing for a uterine fundus that the initial evaluation and in follow-up treatment, for girls
would suggest undetected pregnancy. Pelvic and biman- who have normal hemoglobin level and hematocrit, the
ual examination is indicated for sexually active patients content of hemoglobin in the reticulocyte is a sensitive
to screen for cervicitis and pelvic inflammatory disease. indicator of iron deficiency and can give clinicians more
In virginal patients who have longstanding ongoing information about the tempo of bleeding or recovery of



iron stores. Other laboratory testing may be indicated de- functional, dysmenorrhea is pain that occurs in the ab-
pending on the severity and nature of the symptoms. sence of pelvic disease, whereas secondary dysmenorrhea
For those patients with hemorrhage from menarche or is secondary to a pathologic process. Primary dysmenor-
serious bleeding at any time, coagulation studies includ- rhea is more common than secondary dysmenorrhea, but
ing prothrombin time/international normalized ratio, clinicians should be familiar with “red flags” on history
partial thromboplastin time, and Von Willebrand panel and examination that should lead them to pursue a diag-
are indicated. For those patients with previous amenor- nosis other than functional pain.
rhea or irregular bleeding, screening for endocrinopathies Primary dysmenorrhea usually presents in the second
should be conducted by measuring FSH, LH, TSH, and or third gynecologic year, when ovulation becomes more
possibly prolactin, as well as androgen levels for girls with regular. Pain may be reported in the lower abdomen,
signs of hyperandrogenism on examination. For girls pre- back, or upper thighs. The pain may be associated with
senting with focal pain or a pelvic mass, abdominal ultra- headache, nausea, or diarrhea. The symptoms are caused
sonography also is warranted. by prostaglandin E2 and F2a secretion in the uterus after
Treatment of abnormal vaginal bleeding is based an ovulatory cycle, resulting in increased uterine contrac-
largely on the severity of anemia, in addition to manage- tility and upregulation of pain receptors.
ment of any comorbid conditions. The preferred treat- Nonsteroidal anti-inflammatory drugs (NSAIDs),
ment of vaginal bleeding in adolescence is medical; such as ibuprofen and naproxen, inhibit cyclooxyge-
surgical intervention rarely is indicated. All treatment nase, an enzyme necessary for prostaglandin synthesis.
of vaginal bleeding resulting in anemia must include iron NSAIDs are used commonly to treat dysmenorrhea
replacement, although this therapy can be overlooked and have been shown to be effective in randomized con-
easily during the acute presentation and management. trolled trials. It is important to know that acetaminophen
The general goal of treatment is to stabilize the endo- does not act on this pathway and is much less effective for
metrium by providing estrogen for initial hemostasis and the treatment of primary dysmenorrhea. Traditional rec-
progestins for endometrial stability. The most convenient ommendations for rest, exercise, and proper nutrition
and effective option in most cases is treatment by using have not been shown to be effective.
combined OCPs (Table 3). Sudden withdrawal of either Primary dysmenorrhea may result in significant school
estrogen or progestin may trigger ongoing bleeding, so absence and lost productivity, so aggressive and evidence-
treatment for several months usually is warranted. based treatment is warranted. If appropriate doses of
Long-term follow-up for conditions predisposing to ab- NSAIDs (Table 4) do not control symptoms after two
normal bleeding, such as PCOS, is necessary as well. to three cycles, a trial of OCPs may be indicated. OCPs
For adolescents who have contraindications to the use reduce menstrual pain by eliminating ovulation and by
of estrogen, such as a history of blood clot, uncontrolled thinning the endometrial lining; when ovulation does
hypertension, migraine with aura, immobility, or chronic not occur and the endometrial lining is thinner, the syn-
illness, management of abnormal bleeding with cyclic thesis of prostaglandins is reduced. In severe cases, ex-
progestins often is possible, although sometimes more tended cycle OCP regimens (eg, 84 active pills, followed
challenging. Progestin-eluting IUDs may be an option by 7 placebos) may be used to eliminate menses. Young
in some cases. women with dysmenorrhea often try over-the-counter med-
Menstrual suppression by using GnRH analogs is desir- ications, including ibuprofen and naproxen, and comple-
able in some conditions, but because of the initial agonist mentary therapies such as vitamins and herbal remedies.
phase, withdrawal bleeding often occurs at 3 weeks before Pediatric clinicians should therefore ask specifically about pre-
amenorrhea is established. For this reason, prophylactic use vious treatments before prescribing additional medications.
is better than use in an acute emergency. Antifibrinolytics Before assuming a patient has primary dysmenorrhea,
such as tranexamic acid interfere with the breakdown of the clinician should consider possible causes of secondary
blood clots and thus stop or slow down bleeding; these dysmenorrhea. Patients who continue to experience sig-
agents may be an option in some adolescents with bleeding nificant pain despite 3 to 6 months of OCP use have a
disorders; consultation with a hematologist is suggested. significantly higher risk of endometriosis (presence of en-
dometrial tissue outside the uterus) and should be referred
to a pediatric gynecologist for evaluation. Laparoscopy is
Dysmenorrhea the only definitive way to diagnose endometriosis, but of-
Dysmenorrhea is common in young women worldwide ten it is difficult to recognize this condition in pediatric
and occurs in the majority of adolescents. Primary, or patients.



Table 3. Suggested Combined OCP Regimens for Abnormal Bleeding
Use a monophasic OCP such as:
• Norgestrel 0.3 mg/ethinyl estradiol 30 mg (Lo/Ovral, Low-Ogestrel, Cryselle).a
• Levonorgestrel 0.15 mg/ethinyl estradiol 30 mg (Nordette, Levlen, Levora, Portia).a
For all patients:
• Advise the patient to keep a menstrual calendar.
• Ensure iron stores are addressed. Patients typically need several months of oral iron supplementation to replete iron stores,
and then should be instructed in maintenance of iron needs.
• If OCPs are used for treatment and then discontinued, consider cyclic progestin therapy to prevent recurrences.
A. For mild bleeding—menses slightly prolonged or cycle slightly more frequent, without anemia (Hgb normal):
• May be observed for several cycles and provided treatment with iron and NSAIDs such as ibuprofen or naproxen sodium.
• Consider treatment with OCP or progestin.
• If choose to treat with OCP: 1 pill daily for 21 d, followed by 1 wk of placebo pills or 1 hormone pill continuously for 84-
day cycles or longer.
• Continue this regimen for 3–6 mo.b
B. For moderate bleeding—menses lasting >7 d or cycle frequency <3 wk and mild anemia (Hgb 10–11 g/dL):
• If the patient is not bleeding significantly at the time of the visit, is not already on hormonal therapy, and anemia is mild:
1 pill a day for 21 d is a reasonable first step.
• If patient is bleeding moderately at time of visit: 1 pill twice a day until bleeding stops, followed by 1 hormonal pill a day
for at least 21 d is a reasonable first step.
• If bleeding is under control, continue cyclic 21 day or may elect extended cycles for 3–6 mo.b
• Follow serial Hgbs, as needed; if bleeding persists, may need to continue twice-daily pill for a short interval.
C. For severe bleeding with moderate anemia (Hgb 8–10 g/dL)
• Consider inpatient admission unless patient’s bleeding is slowing and family is reliable, has transportation, and is reachable
by phone.
• For severe bleeding: 1 pill four times a day for 2–4 d, with antiemetic as needed 2 h before each pill; followed by 1 pill
three times a day for 3 d; and then 1 pill twice a day for at least 2 wk. (For this regimen, prescribing OCPs “four times
a day” should be written as “1 pill every 6 hours” and “3 times a day” as “1 pill every 8 hours” in order to maintain
hormonal concentrations.)
• For bleeding that is slowing and Hgb >9 g/dL: 1 pill twice a day can be initiated as a first step.
• Follow closely with serial Hgb; if anemia or bleeding persists, may need to continue twice-daily hormonal pill and
eliminate pill-free interval until Hgb has returned to normal.
• Once Hgb has normalized, cycle using 21 once-daily pills and 5–7 d of placebo or extended cycles for 6 mo.b
D. Severe bleeding with severe anemia (Hgb £7 g/dL, orthostatic vital signs):
• Admit for inpatient management. Transfusion needs are individualized on the basis of Hgb, orthostatic symptoms, amount
of ongoing bleeding, and the ability to gain control of the bleeding.
• Most patients can be treated with OCPs: 1 pill every 4–6 h until bleeding slows (usually takes 24–36 h), with antiemetics
as needed; 1 pill four times a day for 2–4 d; 1 pill three times a day for 3 d; 1 pill twice a day until hematocrit is >30%.
• Occasionally intravenous conjugated estrogens (Premarin) 25 mg every 4 h for 2–3 doses are used in severe acute
hemorrhage. It is very important to remember that the estrogen will stop the bleeding but if a progestin is not added, a re-
bleed from estrogen withdrawal will occur when the IV estrogen is discontinued.
• Consider antifibrinolytic therapy.
• Once Hgb has normalized, cycle using 21 once-daily pills and 5–7 d of placebo or use extended cycles for 6–12 mo.b
Reprinted with permission from Gray SH, Emans SJ. Abnormal vaginal bleeding in the adolescent. In: Emans SJ, Laufer MR, eds. Emans, Laufer, and
Goldstein’s Pediatric and Adolescent Gynecology. 6th ed. Philadelphia, PA: Lippincott, Williams, and Wilkins; 2011:159–167. Hgb¼hemoglobin.
a
Mention of brand name does not imply endorsement of a particular product.
b
It is important to reconsider a patient’s need for birth control before discontinuing OCP therapy.

Other red flags include pelvic pain or bleeding that oc- reveal evidence of an IUD; non-hormone-containing IUDs
curs midcycle and pain associated with vaginal discharge, may increase menstrual pain significantly. Again, urine preg-
all of which may be associated with pelvic infections. nancy testing is always worthwhile because adolescents may
Clinicians should have a low threshold for sending nucleic mistake bleeding in early pregnancy for a period.
acid amplification testing for gonorrhea and C trachomatis In adolescents who have dysmenorrhea from menarche
and doing a speculum and bimanual examination to screen that progresses steadily, genital tract abnormalities with
for pelvic inflammatory disease. Pelvic examination also may obstruction should be considered, as well as endometriosis.



Medications Used to Treat
Table 4.
be weighed, although the absolute risk is low. Transder-
mal contraceptive patches may have a higher associated
Dysmenorrhea risk of blood clot. Medroxyprogesterone injection also
may be of limited use in these patients due to the potential
Propionic Acid Group:
additive risk of low bone density with immobility, as well as
• Ibuprofen 400–600 mg Q 4–6 H weight gain that may further limit mobility.
• Naproxen sodium 550 mg load, then Progestin implants offer long lasting and reversible
275 mg Q 6 H
• Naproxen 500 mg load, then 250 mg
contraception and sometimes can result in amenorrhea
Q 6–8 H but carry a risk of unpredictable bleeding, as do progestin
Fenamate Group: eluting IUDs, and both may require placement under an-
• Mefenamic acid 500 mg loading dose, then esthesia. Hysterectomy and endometrial ablation are
250 mg Q 6 H more likely to result in amenorrhea but would be recom-
Reprinted with permission from Braverman PK, Sondheimer SJ. mended only in very unusual circumstances.
Menstrual disorders. Pediatr Rev. 1997;18(1):25.

Summary
Other causes of pelvic pain not associated with menstrual
problems are beyond the scope of this review. • The presence of normal menses in young women
should be considered a vital sign; heavy, painful,
absent, or irregular menses should be investigated.
Young Women With Special Health-Care (Based on some research evidence as well as
Needs consensus.) (1)(2)
Young women with special health-care needs and their fam- • Patients who are pregnant usually present with
ilies may need particular care with respect to normal men- secondary amenorrhea but may present with irregular
or heavy menstrual bleeding. A sensitive urine
struation as well as menstrual disorders. When possible, the
pregnancy test should be performed early in the
patient’s concerns should be expressed privately and remain evaluation of these complaints, regardless of stated
confidential. It is important that pediatric practitioners not sexual history. (Based on expert opinion.)
assume that young women with disabilities, cognitive or • Menstrual complaints such as heavy bleeding and
otherwise, are not sexually active. Patients’ ability to con- dysmenorrhea are a frequent cause of school absence
in girls and should be evaluated and treated. (Based on
sent to sexual activity should be assessed and discussed
some research evidence as well as consensus.) (1)(2)
openly with parents when appropriate. Many parents have • Polycystic ovary syndrome (PCOS) is a frequent cause
fears about their daughters’ vulnerability to coerced sex and of secondary amenorrhea or oligomenorrhea but also
deserve the opportunity to discuss these concerns. can present with anovulatory and frequent menses.
Normal menses may cause problems of hygiene for (Based on expert opinion.)
• Functional hypothalamic amenorrhea is associated
girls with limited cognitive skills or limited mobility.
commonly with stress, weight change, chronic illness,
Painful menses cause unnecessary suffering, and some and intense athletic activity. Patients with eating
conditions (eg, seizures, headaches) may be triggered disorders have an energy deficit, as do many of those
or worsened by menstrual changes. Treatments to de- experiencing intense athletic activity, and are at risk
crease, eliminate, or make bleeding more predictable for hypothalamic amenorrhea.
• The morbidity associated with prolonged amenorrhea
should be “safe, minimally invasive, and nonpermanent”
is low bone density due to inadequate estrogen
according to the 2009 American Congress of Obstetri- production. Use of oral contraceptives (OCPs) alone
cians and Gynecologists Committee Opinion on men- appears not to restore bone density in girls with
strual manipulation for adolescents with disabilities. anorexia nervosa. The best recommendation is
(10) Total amenorrhea may be difficult to obtain, and increased energy intake and weight gain when
underweight. (Based on some research evidence as
some patients and families may decide that it is easier
well as consensus.) (6)
to manage bleeding that is predictable but potentially • Young women with special health-care needs need
longer, rather than bleeding that is sporadic and irregular. assessment and counseling about sexuality and
NSAIDs may play a useful role in reducing pain and reproductive health. Clinicians should be aware of how
bleeding, as may combined OCPs, used traditionally or cognitive or mobility issues affect menstrual hygiene
and should present options for medical management
in extended or continuous regimens. For young
of menses to improve quality of life. (Based on expert
women with limited mobility, the potential increased opinion.) (10)
risk of deep vein thrombosis with estrogen use should



ACKNOWLEDGEMENTS. The author wishes to thank practice: a study from the Pediatric Research in Office Settings
Ms Alison Clapp for her assistance with review of the liter- network. Pediatrics. 1997;99(4):505–512
6. Gordon CM. Clinical practice. Functional hypothalamic amen-
ature, as well as Drs S. Jean Emans and Gregory F. Hayden
orrhea. N Engl J Med. 2010;363(4):365–371
for their helpful suggestions regarding this article. 7. Zadawski J, Dunaif A. Diagnostic Criteria for Polycystic Ovary
Syndrome: Towards a Rational Approach. Oxford, England: Black-
well Scientific Publications; 1992
References 8. Rotterdam ESHRE/ASRM-Sponsored PCOS consensus work-
1. Diaz A, Laufer MR, Breech LL; American Academy of Pediatrics shop group. Revised 2003 consensus on diagnostic criteria and
Committee on Adolescence; American College of Obstetricians and long-term health risks related to polycystic ovary syndrome
Gynecologists Committee on Adolescent Health Care. Menstrua- (PCOS). Hum Reprod. 2004;19(1):41–47
tion in girls and adolescents: using the menstrual cycle as a vital 9. Azziz R, Carmina E, Dewailly D, et al; Androgen Excess Society.
sign. Pediatrics. 2006;118(5):2245–2250 Positions statement: criteria for defining polycystic ovary syndrome as
2. ACOG Committee on Adolescent Health Care. ACOG Com- a predominantly hyperandrogenic syndrome: an Androgen Excess
mittee Opinion No. 349, November 2006: Menstruation in girls Society guideline. J Clin Endocrinol Metab. 2006;91(11):4237–4245
and adolescents: using the menstrual cycle as a vital sign. Obstet 10. American College of Obstetricians and Gynecologists Com-
Gynecol. 2006;108(5):1323–1328 mittee on Adolescent Health Care. ACOG Committee Opinion
3. Chumlea WC, Schubert CM, Roche AF, et al. Age at menarche No. 448: Menstrual manipulation for adolescents with disabilities.
and racial comparisons in US girls. Pediatrics. 2003;111(1):110–113 Obstet Gynecol. 2009;114(6):1428–1431
4. Sun SS, Schubert CM, Chumlea WC, et al. National estimates of
the timing of sexual maturation and racial differences among US
children. Pediatrics. 2002;110(5):911–919 Suggested Reading
5. Herman-Giddens ME, Slora EJ, Wasserman RC, et al. Second- Braverman PK, Sondheimer SJ. Menstrual disorders. Pediatr Rev.
ary sexual characteristics and menses in young girls seen in office 1997;18(1):17–25, quiz 26

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1. A mother brings in her daughter because of a concern that she has never menstruated. The patient is thin,
athletic, and has a normal physical examination (including genital inspection). At what minimum age does
this concern warrant further investigation?
A. 13 years.
B. 14 years.
C. 15 years.
D. 16 years.
E. 17 years.
2. A 14-year-old girl comes in with a history of monthly cyclical abdominal pain. On examination, you note
midline tenderness in the area below the umbilicus, and a purplish bulging at the vaginal introitus. Of the
following, the most likely diagnosis is:
A. Androgen insensitivity syndrome.
B. Chlamydial infection.
C. Crohn disease.
D. Hematocolpos.
E. Ovarian torsion.



3. A 15-year-old girl comes in for evaluation of infrequent menstrual periods. On examination, you note a BMI of
35 and acne. Otherwise, her examination is unremarkable. Of the following, what is the most likely laboratory
abnormality associated with this patient’s presentation?
A. Elevated follicular stimulating hormone (FSH).
B. Elevated free testosterone.
C. Elevated gonadotropic releasing hormone (GnRH).
D. Elevated prolactin.
E. Elevated thyroid stimulating hormone.

4. A 16-year-old girl is seen with a complaint of excessive bleeding with menses (menorrhagia). Of the following,
which component of the history and examination most suggests von Willebrand disease?
A. Anovulatory cycles.
B. Heavy ﬂow from time of initial menses.
C. Breakthrough bleeding in between periods.
D. Previous oral contraceptive use.
E. Tenderness on bimanual examination.

5. Of the following, which is the most appropriate ﬁrst-line therapy for primary dysmenorrhea?
A. Acetaminophen.
B. Ibuprofen.
C. Metronidazole.
D. Oral contraceptive trial.
E. Relaxation techniques.


Menstrual Disorders
Susan Hayden Gray
Pediatrics in Review 2013;34;6
DOI: 10.1542/pir.34-1-6

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